Global profiling of alternative splicing events and gene expression regulated by hnRNPH/F

In this study, we have investigated the global impact of heterogeneous nuclear Ribonuclear Protein (hnRNP) H/F-mediated regulation of splicing events and gene expression in oligodendrocytes. We have performed a genome-wide transcriptomic analysis at the gene and exon levels in Oli-neu cells treated with siRNA that targets hnRNPH/F compared to untreated cells using Affymetrix Exon Array. Gene expression levels and regulated exons were identified with the GenoSplice EASANA algorithm. Bioinformatics analyses were performed to determine the structural properties of G tracts that correlate with the function of hnRNPH/F as enhancers vs. repressors of exon inclusion. Different types of alternatively spliced events are regulated by hnRNPH/F. Intronic G tracts density, length and proximity to the 5\u27 splice site correlate with the hnRNPH/F enhancer function. Additionally, 6% of genes are differently expressed upon knock down of hnRNPH/F. Genes that regulate the transition of oligodendrocyte progenitor cells to oligodendrocytes are differentially expressed in hnRNPH/F depleted Oli-neu cells, resulting in a decrease of negative regulators and an increase of differentiation-inducing regulators. The changes were confirmed in developing oligodendrocytes in vivo. This is the first genome wide analysis of splicing events and gene expression regulated by hnRNPH/F in oligodendrocytes and the first report that hnRNPH/F regulate genes that are involved in the transition from oligodendrocyte progenitor cells to oligodendrocytes

Proyecto educativo de centro. Una alternativa real

Los diagnósticos que se han realizado a nivel de nuestro sistema educativo señalan, como relevante, un centralismo administrativo y pedagógico junto con una estructura de financiamiento deficitaria. Estas evidencias que afectan, en mayor y menor medida, a muchos centros educativos en la actualidad (públicos o privados) provocan que los mismos no lleguen a constituirse en una identidad convocarte e integradora de su comunidad educativa

Annual killifish adaptations to ephemeral environments: diapause I in two Austrolebias species

Background: Many organisms are able to survive in extreme environments by entering a state of dormancy. In dormancy, vital activities are reduced until environmental conditions are compatible with active life. Annual killifishes show a special developmental pattern characterized by a phase of dispersion-reaggregation of the blastomeres that separates epiboly from organogenesis, and the capability to enter dormancy in diapause. High tolerance to environmental stress confers annual killifish embryos the condition of extremophiles. At present, the questions of our research group are focused on the understanding of the mechanisms involved in diapause regulation through an interdisciplinary approach. As a first step, it is necessary to characterize diapauses at orphological and physiological levels and to evaluate induction cues under laboratory conditions. In this context, we characterized diapause I in two Austrolebias species. Results: Our experimental approach to induce apause I was successful and revealed the co-existence of two diapause I phenotypes named A and B instead of one. These phenotypes showed a tendency for lower total extractable RNA content compared with active developmental stages (80–100% epiboly and early reaggregate). Conclusions: These phenotypes are alternative diapause I stages and may have ecological relevance because both were found in embryos in natural ponds. Developmental Dynamics 246:848–857, 2017. VC 2017 Wiley Periodicals, Inc.CSIC: 147_C61034

Amplifying the Effects of Contrast Agents on Magnetic Resonance Images Using a Deep Learning Method Trained on Synthetic Data

OBJECTIVES: Artificial intelligence (AI) methods can be applied to enhance contrast in diagnostic images beyond that attainable with the standard doses of contrast agents (CAs) normally used in the clinic, thus potentially increasing diagnostic power and sensitivity. Deep learning-based AI relies on training data sets, which should be sufficiently large and diverse to effectively adjust network parameters, avoid biases, and enable generalization of the outcome. However, large sets of diagnostic images acquired at doses of CA outside the standard-of-care are not commonly available. Here, we propose a method to generate synthetic data sets to train an "AI agent" designed to amplify the effects of CAs in magnetic resonance (MR) images. The method was fine-tuned and validated in a preclinical study in a murine model of brain glioma, and extended to a large, retrospective clinical human data set. MATERIALS AND METHODS: A physical model was applied to simulate different levels of MR contrast from a gadolinium-based CA. The simulated data were used to train a neural network that predicts image contrast at higher doses. A preclinical MR study at multiple CA doses in a rat model of glioma was performed to tune model parameters and to assess fidelity of the virtual contrast images against ground-truth MR and histological data. Two different scanners (3 T and 7 T, respectively) were used to assess the effects of field strength. The approach was then applied to a retrospective clinical study comprising 1990 examinations in patients affected by a variety of brain diseases, including glioma, multiple sclerosis, and metastatic cancer. Images were evaluated in terms of contrast-to-noise ratio and lesion-to-brain ratio, and qualitative scores. RESULTS: In the preclinical study, virtual double-dose images showed high degrees of similarity to experimental double-dose images for both peak signal-to-noise ratio and structural similarity index (29.49 dB and 0.914 dB at 7 T, respectively, and 31.32 dB and 0.942 dB at 3 T) and significant improvement over standard contrast dose (ie, 0.1 mmol Gd/kg) images at both field strengths. In the clinical study, contrast-to-noise ratio and lesion-to-brain ratio increased by an average 155% and 34% in virtual contrast images compared with standard-dose images. Blind scoring of AI-enhanced images by 2 neuroradiologists showed significantly better sensitivity to small brain lesions compared with standard-dose images (4.46/5 vs 3.51/5). CONCLUSIONS: Synthetic data generated by a physical model of contrast enhancement provided effective training for a deep learning model for contrast amplification. Contrast above that attainable at standard doses of gadolinium-based CA can be generated through this approach, with significant advantages in the detection of small low-enhancing brain lesions.</p

The role of anaemia in oxidative and genotoxic damage in transfused β-thalassaemic patients.

Redox imbalance and genotoxic damage are commonly observed in β thalassaemic patients. The aim of this study was to assess the role of anaemia in oxidative and genotoxic damage in regularly transfused thalassaemic patients, undergoing iron chelation therapy.We studied the relationships of haematological, biochemical and clinical parameters with oxidative (reactive oxygen species and 8-oxo-7,8-dihydro-2'-deoxyguanosine) and genotoxic biomarkers (Comet assay and cytokinesis-block micronucleus test) in blood samples from 105 patients. To reduce the early effect of redox-active iron, samples were collected when pharmacokinetics of the iron chelators ensured their maximum effectiveness. The transfusion regimen, cardiac and hepatic magnetic resonance imaging T2* were evaluated to characterize the patient cohort. Labile plasma iron (LPI) was also assayed.Haemoglobin level had a significant effect on ROS, %DNA in the tail and micronuclei-micronucleated cell frequency (p  0.05). Higher Hb values reduced redox imbalance. LPI, detectable in 50.5% of patients, was related to the number of apoptotic and necrotic lymphocytes (p = 0.03), demonstrating the cytotoxic effect of iron.The results highlight that an adequate transfusion regimen is essential to limit oxidative and genotoxic damage in β-thalassemic patients undergoing chelation therapy.Owing to the higher risk of cancer in the thalassaemic cohorts, specific genotoxicity/oxidative biomarkers should be monitored in order to ameliorate and formulate more personalized disease management

Evidence for a Novel Reaction Mechanism of a Prompt Shock-Induced Fission Following the Fusion of 78Kr and 40Ca Nuclei at E/A =10 MeV

An analysis of experimental data from the inverse-kinematics ISODEC experiment on 78Kr+40Ca reaction at a bombarding energy of 10 AMeV has revealed signatures of a hitherto unknown reaction mechanism, intermediate between the classical damped binary collisions and fusion-fission, but also substantially different from what is being termed in the literature as fast fission or quasi fission. These signatures point to a scenario where the system fuses transiently while virtually equilibrating mass asymmetry and energy and, yet, keeping part of the energy stored in a collective shock-imparted and, possibly, angular momentum bearing form of excitation. Subsequently the system fissions dynamically along the collision or shock axis with the emerging fragments featuring a broad mass spectrum centered around symmetric fission, relative velocities somewhat higher along the fission axis than in transverse direction, and virtually no intrinsic spin. The class of massasymmetric fission events shows a distinct preference for the more massive fragments to proceed along the beam direction, a characteristic reminiscent of that reported earlier for dynamic fragmentation of projectile-like fragments alone and pointing to the memory of the initial mass and velocity distribution.Comment: 5 PAGES, 6 FIGURE

A χ2\chi^2 veto for continuous gravitational wave searches

$\chi^2$ vetoes are commonly used in searching for gravitational waves, in particular for broad-band signals, but they can also be applied to narrow-band continuous wave signals, such as those expected from rapidly rotating neutron stars. In this paper we present a $\chi^2$ veto adapted to the Hough transform searches for continuous gravitational wave signals; we characterize the $\chi^2$-significance plane for different frequency bands; and discuss the expected performance of this veto in LIGO analysis.Comment: Final version, 12th Gravitational Waves Data Analysis Worksho

Correlations between isospin dynamics and Intermediate Mass Fragments emission time scales: a probe for the symmetry energy in asymmetric nuclear matter

We show new data from the $^{64}$Ni+$^{124}$Sn and $^{58}$Ni+$^{112}$Sn reactions studied in direct kinematics with the CHIMERA detector at INFN-LNS and compared with the reverse kinematics reactions at the same incident beam energy (35 A MeV). Analyzing the data with the method of relative velocity correlations, fragments coming from statistical decay of an excited projectile-like (PLF) or target-like (TLF) fragments are discriminated from the ones coming from dynamical emission in the early stages of the reaction. By comparing data of the reverse kinematics experiment with a stochastic mean field (SMF) + GEMINI calculations our results show that observables from neck fragmentation mechanism add valuable constraints on the density dependence of symmetry energy. An indication is found for a moderately stiff symmetry energy potential term of EOS.Comment: Talk given by E. De Filippo at the 11th International Conference on Nucleus-Nucleus Collisions (NN2012), San Antonio, Texas, USA, May 27-June 1, 2012. To appear in the NN2012 Proceedings in Journal of Physics: Conference Series (JPCS